Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PBRM-1/PBAF-regulated genes in a multipotent progenitor in C. elegans

ABSTRACT: The Caenorhabditiselegans somatic gonadal precursors (SGPs) are multipotent progenitors that generate all somatic cells of the adult reproductive system. The two SGPs originate in the mesodermal layer and are born through a division that produces one SGP and one head mesodermal cell (hmc). One hmc terminally differentiates and the other dies by programmed cell death. The PBAF chromatin remodeling complex promotes the multipotent SGP fate. Complete loss of PBAF causes lethality, so we used a combination of Cre/lox recombination and GFP nanobody-directed protein degradation to eliminate PBRM-1, the signature subunit of the PBAF complex, from 83 mesodermal cells, including SGPs, body muscles, and the hmc. We used RNA sequencing to identify genes acting downstream of PBAF in these cells and identified 1955 transcripts that were significantly differentially expressed between pbrm-1(-) and pbrm-1(+) in the mesoderm of L1 larvae.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE249603 | GEO | 2023/12/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Structure of nucleosome-bound human PBAF complex

Project description:BAF and PBAF are mammalian SWI/SNF family chromatin remodeling complexes that possess multiple histone/DNA-binding subunits and create nucleosome-depleted/free regions for transcription activation. Despite previous structural studies and recent advance of SWI/SNF family complexes, it remains incompletely understood how PBAF-nucleosome complex is organized. Here we determined structure of 13-subunit human PBAF in complex with acetylated nucleosome in ADP-BeF3-bound state. Four PBAF-specific subunits work together with nine BAF/PBAF-shared subunits to generate PBAF-specific modular organization, distinct from that of BAF at various regions. PBAF-nucleosome structure reveals six histone-binding domains and four DNA-binding domains/modules, the majority of which directly bind histone/DNA. This multivalent nucleosome-binding pattern, not observed in previous studies, suggests that PBAF may integrate comprehensive chromatin information to target genomic loci for function. Our study reveals molecular organization of subunits and histone/DNA-binding domains/modules in PBAF-nucleosome complex and provides structural insights into PBAF-mediated nucleosome association complimentary to the recently reported PBAF-nucleosome structure.

2023-03-11 | PXD036708 | Pride

PHF10 subunit of PBAF complex mediates transcriptional activation by MYC

Project description:The PBAF complex, a member of SWI/SNF family of chromatin remodelers, plays an essential role in transcriptional regulation. We revealed a disease progression associated elevation of PHF10 subunit of PBAF in clinical samples of melanoma. We demonstrated that in melanoma cell lines, PHF10 interacts with MYC and facilitates the recruitment of PBAF complex to target gene promoters, therefore augmenting MYC transcriptional activation of genes involved in the cell cycle progression. Depletion of either PHF10 or MYC induced G1 accumulation and a senescence-like phenotype. Our data identify PHF10 as a pro-oncogenic mechanism and an essential novel link between chromatin remodeling and MYC-dependent gene transcription.

2021-04-08 | GSE164726 | GEO

Specific PBAF complex (dcPBAF) containing PHF10 lacking DPF maintains transcription in differentiated neurons

Project description:The PBAF chromatin-remodeling complex is essential for transcription in mammalian cells. We found that PHF10 specific subunit of PBAF lacking C-terminal DPF is expressed in neurons of adult mouse and human brain. We purified the neuronal PBAF of newborn and adult mouse brain using antibodies against PHF10. We found that specific PBAF, designated as dcPBAF, is dominant in mature neurons. dcPBAF is associated with TAF4, TAF5, TAF6, TAF9 subunits of TFIID, does not contain BRD7 and is characterized by the presence of PHF10 isoform lacking N-terminal amino acids and DPF. The dcPBAF binds promoters of actively transcribed housekeeping and neuron specific genes in terminally differentiated neurons of adult mouse. It maintains high transcription level of neuron specific genes in differentiated human neuronal cell. These data indicate some specific features of PBAF mediated chromatin in terminally differentiated mammalian cells.

2022-08-30 | GSE199351 | GEO

PBAF complex deficiency in melanoma mediates BAF occupancy and transcription factor dynamics (Chromatin)

Project description:ARID2 is an essential subunit of the SWI/SNF PBAF chromatin remodeler and is highly mutate in melanoma. To elucidate the role of ARID2 in melanoma biology and chromatin structure we utilized CRISPR Cas9 methodology to generate isogenic ARID2 WT and KO melanoma clonal cell lines. We further map the genomic localization of several SWI/SNF subunits, open and repressed chromatin markers, and multiple transcription factors to characterize how loss of the PBAF subcomplex alters chromatin accessibility and the melanoma transcription factor network. Finally, we characterized the transcriptional changes produced by PBAF depletion.

2022-04-05 | GSE172383 | GEO

PBAF complex deficiency in melanoma mediates BAF occupancy and transcription factor dynamics (RNA-Seq)

2022-04-05 | GSE172384 | GEO

Circadian lncRNA ADIRF-AS1 binds PBAF and regulates renal clear cell tumorigenesis

Project description:We identified ADIRF-AS1 as a BMAL1-CLOCK regulated circadian lncRNA. Loss of ADIRF-AS1 in U2OS cells altered rhythmicity of clock-controlled genes and expression of genes associated with cell adhesion and the extracellular matrix (ECM) but did not affect neighboring genes in cis. Affinity based enrichment of U2OS ADIRF-AS1-interacting proteins identified all components of the tumor suppressive PBAF (PBRM1/BRG1) complex. Because PBRM1 is a tumor suppressor mutated in 40% of clear cell renal carcinoma (ccRCC) cases, we studied ccRCC 786O cells and also found PBRM1 bound to ADIRF-AS1. Reducing ADIRF-AS1 expression in 786O and A498 ccRCC cells decreased expression of PBAF-suppressed genes, consistent with ADIRF-AS1 acting to antagonize the function of PBAF. Loss of PBRM1, however, rescued PBAF responsive cell cycle genes in ADIRF-AS1 KO 786O ccRCC cells. Importantly, ADIRF-AS1 expression correlates with survival in human ccRCC, particularly in PBRM1 wild-type, but not mutant PBRM1 tumors. In this regard, loss of ADIRF-AS1 did not affect in vitro 786O cell growth, but strikingly eliminated in vivo tumorigenesis, which was partially rescued by concurrent loss of PBRM1. This rescue, however, requires Matrigel, suggesting a PBRM1-independent function of ADIRF-AS1 in regulating the ECM. Collectively, our findings suggest that ADIRF-AS1 functions partly to antagonize the tumor suppressive effect of the PBAF complex and behaves as an unforeseen BMAL1-regulated, oncogenic lncRNA.

2022-11-16 | GSE199825 | GEO

Loss of PBAF Promotes Effector Differentiation and Limits CD8+ T Cell Exhaustion in Chronic Viral Infection and Cancer [multiomics]

Project description:To gain insights into how PBAF complex regulates dynamic chromatin structure changes in LCMV-specific CD8+ T cells during chronic viral infection and examine the how PBAF-deficiency alters the transcriptional and epigenetic heterogeneity of CD8+ T cells, we performed single cell RNA + ATAC multiomic sequencing on Arid2- and Pbrm1-deficient CD8+ T cells and their wild-type counterpart.

2023-06-22 | GSE222346 | GEO

Brd7, a novel PBAF-specific SWI/SNF subunit, is required for gene activation and repression in embryonic stem cells

Project description:The composition of chromatin remodeling complexes dictates how these enzymes control transcriptional programs and cellular identity. Here, we investigate the composition of SWI/SNF complexes in embryonic stem cells (ESCs). In contrast to differentiated cells, ESCs have a biased incorporation of certain paralogous SWI/SNF subunits, with low levels of Brm, BAF170 and ARID1B. Upon differentiation, the expression of these subunits increases, resulting in a higher diversity of compositionally distinct SWI/SNF enzymes. We also identify Brd7 as a novel component of the PBAF complex in both ESCs and differentiated cells. Using shRNA-mediated depletion of Brg1, we show that SWI/SNF can function as both a repressor and an activator in pluripotent cells, regulating expression of developmental modifiers and signaling components such as Nodal, ADAMTS1, Bmi-1, CRABP1 and TRH. Knock-down studies of PBAF-specific Brd7 and of a signature subunit within the BAF complex, ARID1A, show that these two sub-complexes affect SWI/SNF target genes differentially, in some cases even antagonistically. This may be due to their different biochemical properties. Finally, we examine the role of SWI/SNF in regulating its target genes during differentiation. We find that SWI/SNF affects recruitment of components of the pre-initiation complex in a promoter-specific manner, to modulate transcription positively or negatively. Taken together, our results provide insight into the function of compositionally diverse SWI/SNF enzymes that underlie their inherent gene-specific mode of action. R1 ESCs were infected in duplicates with shRNA targeting Brg1 or GLUT4 (as a control). Knockdown of Brg1 mRNA affected Brg1 protein levels efficiently. RNA was isolated 67 hours post-infection and analyzed using microarrays.

2010-03-04 | E-GEOD-7791 | biostudies-arrayexpress

Mitochondrial SHMT2 is a crucial therapeutic target in dedifferentiated thyroid cancer

Project description:The roles of the serine/glycine metabolic pathway (SGP) have recently been evident in certain types of tumor physiology; however, the pathological relevance of SGP in undifferentiated thyroid cancer remains unexplored. Herein, we employed a comparative transcriptome analysis of bulk RNA sequencing coupled with single-cell RNA sequencing, showing that the high expression of SHMT2 and MTHFD2 is tightly associated with a low thyroid differentiation score (TDS) and poor clinical features in thyroid cancer. In addition, unique metabolic reprogramming of SGP-relevant pathways in dedifferentiated cancer cells, and a distinct trajectory of a subpopulation of tumor cells with a high mitochondrial one-carbon pathway was observed. More importantly, such dramatic changes are functionally relevant, as inhibition of SHMT2 significantly compromises mitochondrial respiration and decreases tumor size by upregulating TDS markers. Taken together, our results highlight the importance of the mitochondrial one-carbon pathway, including SGP, in undifferentiated thyroid cancer and suggest that SHMT2 is a novel therapeutic target.

2023-10-17 | GSE213647 | GEO

PHF10 subunit of PBAF complex mediates transcriptional activation by MYC

Project description:PHF10 subunit of PBAF complex mediates transcriptional activation by MYC

| PRJNA691744 | ENA